Runx2 heterozygosity alters homeostasis of the periodontal complex.

BACKGROUND AND OBJECTIVE: Haploinsufficiency of Runx2 (Runx2+/- ) causes dental anomalies. However, little is known about the involvement of Runx2 in the maintenance of dentin, cementum, and the periodontal ligament (PDL) during adulthood. This study aimed to observe the effects of Runx2+/- on homeostasis of the periodontal complex. MATERIALS AND METHODS: A total of 14 three-month-old Runx2+/- mice and their wild-type littermates were examined using micro-computed tomography, histology, and immunohistochemistry. Phenotypic alterations in the dentin, cementum, and PDL were characterized and quantified. RESULTS: Haploinsufficiency of Runx2 caused cellular changes in the PDL space including reduction of cell proliferation and apoptosis, and irregular attachment of the collagen fibers in the PDL space into the cementum. Absence of continuous thickness of cementum was also observed in Runx2+/- mice. CONCLUSION: Runx2 is critical for cementum integrity and attachment of periodontal fibers. Because of its importance to cementum homeostasis, Runx2 is essential for homeostasis of periodontal complex.

Development of nucleocapsid-specific monoclonal antibodies for SARS-CoV-2 and their ELISA diagnostics on an automatic microfluidic device.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has threatened public health globally, and the emergence of viral variants has exacerbated an already precarious situation. To prevent further spread of the virus and determine government action required for virus control, accurate and rapid immunoassays for SARS-CoV-2 diagnosis are urgently needed. In this study, we generated monoclonal antibodies (mAbs) against the SARS-CoV-2 nucleocapsid protein (NP), compared their reactivity using an enzyme-linked immunosorbent assay (ELISA), and selected four mAbs designated 1G6, 3E10, 3F10, and 5B6 which have higher reactivity to NP and viral lysates of SARS-CoV-2 than other mAbs. Using an epitope mapping assay, we identified that 1G6 detected the C-terminal domain of SARS-CoV-2 NP (residues 248-364), while 3E10 and 3F10 bound to the N-terminal domain (residues 47-174) and 3F10 detected the N-arm region (residues 1-46) of SARS-CoV-2 NP. Based on the epitope study and sandwich ELISA, we selected the 1G6 and 3E10 Abs as an optimal Ab pair and applied them for a microfluidics-based point-of-care (POC) ELISA assay to detect the NPs of SARS-CoV-2 and its variants. The integrated and automatic microfluidic system could operate the serial injection of the sample, the washing solution, the HRP-conjugate antibody, and the TMB substrate solution simply by controlling air purge via a single syringe. The proposed Ab pair-equipped microsystem effectively detected the NPs of SARS-CoV-2 variants as well as in clinical samples. Collectively, our proposed platform provides an advanced protein-based diagnostic tool for detecting SARS-CoV-2.

Cyclic Peptide Mimotopes for the Detection of Serum Anti-ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma.

Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.

Artificial Intelligent Model With Neural Network Machine Learning for the Diagnosis of Orthognathic Surgery.

Diagnosis and treatment planning are the most important steps in the orthognathic surgery for the successful treatment. The purpose of this study was to develop a new artificial intelligent model for surgery/non-surgery decision and extraction determination, and to evaluate the performance of this model. The sample used in this study consisted of 316 patients in total. Of the total sample, 160 were planned with surgical treatment and 156 were planned with non-surgical treatment. The input values of artificial neural network were obtained from 12 measurement values of the lateral cephalogram and 6 additional indexes. The artificial intelligent model of machine learning consisted of 2-layer neural network with one hidden layer. The learning was carried out in 3 stages, and 4 best performing models were adopted. Using these models, decision-making success rates of surgery/non-surgery, surgery type, and extraction/non-extraction were calculated. The final diagnosis success rate was calculated by comparing the actual diagnosis with the diagnosis obtained by the artificial intelligent model. The success rate of the model showed 96% for the diagnosis of surgery/non-surgery decision, and showed 91% for the detailed diagnosis of surgery type and extraction decision. This study suggests the artificial intelligent model using neural network machine learning could be applied for the diagnosis of orthognathic surgery cases.

Microbial changes in biofilms on composite resins with different surface roughness: An in vitro study with a multispecies biofilm model.

STATEMENT OF PROBLEM: The single-species biofilm method cannot represent the interaction and complex functions of microorganisms associated with oral biofilms. PURPOSE: The purpose of this in vitro study was to investigate microbial changes in biofilms on composite resins of varying surface roughness by using a multispecies biofilm model with early-colonizing streptococci, middle colonizer, and late-colonizing gram-negative anaerobes. MATERIAL AND METHODS: Composite resin disks were prepared with different roughness: SR180, SR400, SR1500, and SRGlass roughened with 180-, 400-, and 1500-grit silicon carbide paper and glass (control surface without surface roughening). Surface roughness was analyzed by confocal laser scanning and scanning electron microscopy. After multispecies biofilms had been grown on the composite resin surfaces, the adhesion of Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and of total bacteria was determined after 1 (T1) and 4 (T2) days. Differences in surface roughness among the 4 groups were tested with 1-way ANOVA. Multifactorial analysis of variance was used to determine the time-related differences in the bacterial composition with respect to surface roughness (α=.05). RESULTS: The order of SR, from highest to lowest, was SR180 (1.45 ±0.11 µm), SR400 (0.62 ±0.05 µm), SR1500 (0.35 ±0.02 µm), and SRGlass (0.15 ±0.01 µm) (SR180>SR400>SR1500>SRGlass, P<.001). Increased surface roughness was not proportional to bacterial adhesion. Significant differences in the adhesion of total bacteria was only found between SRGlass and SR180 (SR180>SRGlass, P=.029). The adhesion of S. mutans and S. sobrinus to SR180 and SR400 was higher than that to SRGlass (SR180=SR400>SRGlass; S. mutans, P=.003; S. sobrinus, P=.002). However, the adhesion of A. actinomycetemcomitans and P. gingivalis to composite resin was not significantly influenced by surface roughness. Adhesion of total bacteria, S. mutans, and S. sobrinus increased from T1 to T2 (T1T2; A. actinomycetemcomitans, P<.001; P. gingivalis, P=.013). CONCLUSIONS: Decreased adhesion of cariogenic streptococci and total bacteria was observed at surface roughness values of around 0.15 µm. Periodic finishing of surface roughness should be considered to minimize the adhesion of cariogenic streptococci to composite resin surfaces.

Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma.

BACKGROUND: Tumor-associated (TA) autoantibodies, which are generated by the immune system upon the recognition of abnormal TA antigens, are promising biomarkers for the early detection of tumors. In order to detect autoantibody biomarkers effectively, antibody-specific epitopes in the diagnostic test should maintain the specific conformations that are as close as possible to those presenting in the body. However, when using patients' serum as a source of TA autoantibodies the characterization of the autoantibody-specific epitope is not easy due to the limited amount of patient-derived serum. METHODS: To overcome these limits, we constructed a B cell hybridoma pool derived from a hepatocellular carcinoma (HCC) model HBx-transgenic mouse and characterized autoantibodies derived from them as tumor biomarkers. Their target antigens were identified by mass spectrometry and the correlations with HCC were examined. With the assumption that TA autoantibodies generated in the tumor mouse model are induced in human cancer patients, the enzyme-linked immunosorbent assays (ELISA) based on the characteristics of mouse TA autoantibodies were developed for the detection of autoantibody biomarkers in human serum. To mimic natural antigenic structures, the specific epitopes against autoantibodies were screened from the phage display cyclic random heptapeptide library, and the streptavidin antigens fused with the specific epitopes were used as coating antigens. RESULTS: In this study, one of HCC-associated autoantibodies derived from HBx-transgenic mouse, XC24, was characterized. Its target antigen was identified as splicing factor 3b subunit 1 (SF3B1) and the high expression of SF3B1 was confirmed in HCC tissues. The specific peptide epitopes against XC24 were selected and, among them, XC24p11 cyclic peptide (-CDATPPRLC-) was used as an epitope of anti-SF3B1 autoantibody ELISA. With this epitope, we could effectively distinguish between serum samples from HCC patients (n = 102) and healthy subjects (n = 85) with 73.53% sensitivity and 91.76% specificity (AUC = 0.8731). Moreover, the simultaneous detection of anti-XC24p11 epitope autoantibody and AFP enhanced the efficiency of HCC diagnosis with 87.25% sensitivity and 90.59% specificity (AUC = 0.9081). CONCLUSIONS: ELISA using XC24p11 peptide epitope that reacts against anti-SF3B1 autoantibody can be used as a novel test to enhance the diagnostic efficiency of HCC.

Alveolar Molding Effect in Infants With Unilateral Cleft Lip and Palate: Comparison of Two- and Three-Dimensional Measurements.

The purpose of this study was to compare the results of two- (2D) and three-dimensional (3D) measurements for the alveolar molding effect in patients with unilateral cleft lip and palate. The sample consisted of 23 unilateral cleft lip and palate infants treated with nasoalveolar molding (NAM) appliance. Dental models were fabricated at initial visit (T0; mean age, 23.5 days after birth) and after alveolar molding therapy (T1; mean duration, 83 days). For 3D measurement, virtual models were constructed using a laser scanner and 3D software. For 2D measurement, 1:1 ratio photograph images of dental models were scanned by a scanner. After setting of common reference points and lines for 2D and 3D measurements, 7 linear and 5 angular variables were measured at the T0 and T1 stages, respectively. Wilcoxon signed rank test and Bland-Altman analysis were performed for statistical analysis. The alveolar molding effect of the maxilla following NAM treatment was inward bending of the anterior part of greater segment, forward growth of the lesser segment, and decrease in the cleft gap in the greater segment and lesser segment. Two angular variables showed difference in statistical interpretation of the change by NAM treatment between 2D and 3D measurements (ΔACG-BG-PG and ΔACL-BL-PL). However, Bland-Altman analysis did not exhibit significant difference in the amounts of change in these variables between the 2 measurements. These results suggest that the data from 2D measurement could be reliably used in conjunction with that from 3D measurement.

Influence of temporomandibular joint disc displacement on craniocervical posture and hyoid bone position.

INTRODUCTION: The purpose of this study was to evaluate craniocervical posture and hyoid bone position in orthodontic patients with temporomandibular joint (TMJ) disc displacement. METHODS: The subjects consisted of 170 female orthodontic patients who consented to bilateral magnetic resonance imaging of their TMJs. They were divided into 3 groups based on the results of magnetic resonance imaging of their TMJs: bilateral normal disc position, bilateral disc displacement with reduction, and bilateral disc displacement without reduction. Twenty-five variables from lateral cephalograms were analyzed with 1-way analysis of variance to investigate differences in craniocervical posture and hyoid bone position with respect to TMJ disc displacement status. Pearson correlation coefficients were calculated to analyze the relationships between craniofacial morphology and craniocervical posture or hyoid bone position. RESULTS: Subjects with TMJ disc displacement were more likely to have an extended craniocervical posture with Class II hyperdivergent patterns. The most significant differences were found between patients with bilateral normal disc position and bilateral disc displacement without reduction. However, hyoid bone position in relation to craniofacial references was not significantly different among the TMJ disc displacement groups, except for variables related to the mandible. Pearson correlation coefficients indicated that extended craniocervical posture was significantly correlated with backward positioning and clockwise rotation of the mandible. CONCLUSIONS: This suggests that craniocervical posture is significantly influenced by TMJ disc displacement, which may be associated with hyperdivergent skeletal patterns with a retrognathic mandible.

Adhesion of mutans streptococci to self-ligating ceramic brackets: in vivo quantitative analysis with real-time polymerase chain reaction.

OBJECTIVE: To analyze in vivo mutans streptococci (MS) adhesion to self-ligating ceramic brackets [Clarity-SL (CSL) and Clippy-C (CC)] and the relationships between bacterial adhesion and oral hygiene indices. MATERIALS AND METHODS: Four central incisor brackets from the maxilla and mandible were collected from 40 patients (20 patients per each bracket type) at debonding immediately after plaque and gingival indices were measured. Adhesions of Streptococcus mutans, S. sobrinus, and total bacteria were quantitatively determined using real-time polymerase chain reaction after genomic DNA was extracted. Factorial analysis of variance was used to analyze bacterial adhesion to the brackets with respect to the bracket type and jaw position. Correlation coefficients were calculated to determine the relationships of bacterial adhesion to oral hygiene indices. RESULTS: Adhesion of total bacteria and S. mutans to CSL was higher than that to CC (P < 0.001). Adhesion of total bacteria to the mandibular brackets was higher than that to the maxillary ones (P < 0.001), while adhesion of S. mutans to the maxillary brackets were higher than that in the mandibular ones (P < 0.001). In particular, the proportion of S. mutans to total bacteria in CSL was higher than CC (P < 0.05) in the maxillary anterior teeth (P < 0.001). There were no significant differences in adhesion of S. sobrinus between the brackets and jaw positions. Interestingly, no significant relationships were found between bacterial adhesions and oral hygiene indices. LIMITATIONS: Complex bracket configurations may significantly influence bacterial adhesion to orthodontic brackets. Further in vivo study using bracket raw materials will help to define the relationships between bacteria adhesion and enamel demineralization. CONCLUSIONS: Because oral hygiene indices were not significantly correlated with adhesions of MS to self-ligating ceramic brackets, careful examinations around the brackets should be needed to prevent enamel demineralization, regardless of oral hygiene status.

The molecular and cellular effects of ageing on the periodontal ligament.

AIM: Many in vitro studies have investigated age-related biological changes in cells comprising the periodontium but the basic question of whether the periodontium can maintain its integrity with age remains unanswered. Thus, the aim of this study was to understand how, in the absence of disease, advancing age impacts the structure of the periodontium. MATERIALS AND METHODS: Of 4, 10, 25, and 50-week-old mice were examined using histology and immunohistochemical analyses for cell proliferation, cell turnover, collagen quantity and quality, osteogenic markers, bone turnover, and cytokine expression. RESULTS: The periodontal ligament (PDL) space shows a gradual decrease in width over the lifespan of the mice. Cell proliferation as well as the quantity and quality of collagen fibres decreased with age although cell density did not appear to be altered. Osteoprogenitor markers in the PDL maintained their expression with increasing age. Alkaline phosphatase (ALP) activity decreased, but osteoclast activity increased with age. CONCLUSIONS: Ageing is associated with a decline in the quality and quantity of collagen and an increase in bone resorption, all of which can diminish the function of the periodontium even in the absence of disease.

Downregulation of Wnt causes root resorption.

INTRODUCTION: There are multiple causes of external root resorption, but absent a disease state, it is most often observed when excessive physical force is used during orthodontic treatment. Even without mechanical stimulation, however, root resorption can still occur. The purpose of this study was to test whether Wnt signaling plays a role in pathologic root resorption, by conditionally deleting Wntless (Wls) from odontoblasts and osteoblasts and then evaluating the phenotypic effects on the maintenance of the root surface. METHODS: Ten (age, 1 month) and 20 (age, 3 months) OCN-Cre;Wls(fl/fl) mice and their wild-type littermates were evaluated using microcomputed tomography, histology, and immunohistochemistry. Phenotypic alterations in the alveolar bone, dentin, and cementum were characterized and quantified. RESULTS: In a genetic model of reduced Wnt signaling, we found that RANKL expression is upregulated, and osteoprotegerin expression is downregulated. This molecular disruption results in an increase in osteoclast activity, a decrease in osteoblast activity, and extensive, spontaneous root resorption. A genetic strain of mice in which Wnt signaling is elevated exhibits thicker cementum, whereas, even in the perinatal period, OCN-Cre;Wls(fl/fl) mice exhibit thinner cementum. CONCLUSIONS: Taken together, these data demonstrate that Wnts regulate cementum homeostasis, and that idiopathic cases of root resorption might have as their etiology a reduction in endogenous Wnt signaling.

S2 Peptide-Conjugated SARS-CoV-2 Virus-like Particles Provide Broad Protection against SARS-CoV-2 Variants of Concern.

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses. Glycan-free S2 peptides were synthesized and attached to SARS-CoV-2 virus-like particles (VLPs) lacking the S antigen. Humoral and cellular immune responses were analyzed after the second booster immunization in BALB/c mice. Enzyme-linked immunosorbent assay revealed the reactivity of sera against SARS-CoV-2 variants, and pseudovirus neutralization assay confirmed neutralizing activities. Among the S2 peptide-conjugated VLPs, the S2.3 (N1135-K1157) and S2.5 (A1174-L1193) peptide-VLP conjugates effectively induced S2-specific serum immunoglobulins. These antisera showed high reactivity against SARS-CoV-2 variant S proteins and effectively inhibited pseudoviral infections. S2 peptide-conjugated VLPs activated SARS-CoV-2 VLP-specific T-cells. The SARS-CoV-2 vaccine incorporating conserved S2 peptides and CoV-2 VLPs shows promise as a universal vaccine capable of generating neutralizing antibodies and T-cell responses against SARS-CoV-2 variants.

Novel S2 subunit-specific antibody with broad neutralizing activity against SARS-CoV-2 variants of concern.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), had a major impact on both the global health and economy. Numerous virus-neutralizing antibodies were developed against the S1 subunit of SARS-CoV-2 spike (S) protein to block viral binding to host cells and were authorized for control of the COVID-19 pandemic. However, frequent mutations in the S1 subunit of SARS-CoV-2 enabled the emergence of immune evasive variants. To address these challenges, broadly neutralizing antibodies targeting the relatively conserved S2 subunit and its epitopes have been investigated as antibody therapeutics and universal vaccines. Methods: We initiated this study by immunizing BALB/c mice with ß-propiolactone-inactivated SARS-CoV-2 (IAV) to generate B-cell hybridomas. These hybridomas were subsequently screened using HEK293T cells expressing the S2-ECD domain. Hybridomas that produced anti-S2 antibodies were selected, and we conducted a comprehensive evaluation of the potential of these anti-S2 antibodies as antiviral agents and versatile tools for research and diagnostics. Results: In this study, we present a novel S2-specific antibody, 4A5, isolated from BALB/c mice immunized with inactivated SARS-CoV-2. 4A5 exhibited specific affinity to SARS-CoV-2 S2 subunits compared with those of other ß-CoVs. 4A5 bound to epitope segment F1109-V1133 between the heptad-repeat1 (HR1) and the stem-helix (SH) region. The 4A5 epitope is highly conserved in SARS-CoV-2 variants, with a significant conformational feature in both pre- and postfusion S proteins. Notably, 4A5 exhibited broad neutralizing activity against variants and triggered Fc-enhanced antibody-dependent cellular phagocytosis. Discussion: These findings offer a promising avenue for novel antibody therapeutics and insights for next-generation vaccine design. The identification of 4A5, with its unique binding properties and broad neutralizing capacity, offers a potential solution to the challenge posed by SARS-CoV-2 variants and highlights the importance of targeting the conserved S2 subunit in combating the COVID-19.

Effects of cleft type, facemask anchorage method, and alveolar bone graft on maxillary protraction: a three-dimensional finite element analysis.

OBJECTIVE: To investigate biomechanical effects of cleft type (unilateral/bilateral cleft lip and palate), facemask anchorage method (tooth-borne and miniplate anchorage), and alveolar bone graft on maxillary protraction. DESIGN: Three-dimensional finite element analysis with application of orthopedic force (30° downward and forward to the occlusal plane, 500 g per side). MODEL: Computed tomography data from a 13.5-year-old girl with maxillary hypoplasia. INTERVENTION: Eight three-dimensional finite element models were fabricated according to cleft type, facemask anchorage method, and alveolar bone graft. MAIN OUTCOME MEASURE(S): Initial stress distribution and displacement after force application were analyzed. RESULTS: Unilateral cleft lip and palate showed an asymmetric pattern in stress distribution and displacement before alveolar bone graft and demonstrated a symmetric pattern after alveolar bone graft. However, bilateral cleft lip and palate showed symmetric patterns in stress distribution and displacement before and after alveolar bone graft. In both cleft types, the graft extended the stress distribution area laterally beyond the infraorbital foramen. For both unilateral and bilateral cleft lip and palate, a facemask with a tooth-borne anchorage showed a dentoalveolar effect with prominent stress distribution and displacement on the upper canine point. In contrast, a facemask with miniplate anchorage exhibited an orthopedic effect with more favorable stress distribution and displacement on the middle maxilla point. In addition, the facemask with a miniplate anchorage showed a larger stress distribution area and sutural stress values than did the facemask with a tooth-borne anchorage. The pterygopalatine and zygomatico-maxillary sutures showed the largest sutural stress values with a facemask with a miniplate anchorage and after alveolar bone grafting, respectively. CONCLUSION: In this three-dimensional finite element analysis, it would be more advantageous to perform maxillary protraction using a facemask with a miniplate anchorage than a facemask with a tooth-borne anchorage and after alveolar bone graft rather than before alveolar bone graft, regardless of cleft type.

Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide­conjugated BSA.

Tumor­associated (TA) autoantibodies are considered to be promising biomarkers for the early detection of cancer, prior to the development of clinical symptoms. In the present study, a novel TA autoantibody was detected, which may prove to be useful as a diagnostic marker of human HCC using an HBx­transgenic (HBx­tg) hepatocellular carcinoma (HCC) mouse model. Its target antigen was identified as the bromodomain­containing protein 2 (BRD2), a transcriptional regulator that plays a pivotal role in the transcriptional control of diverse genes. BRD2 was upregulated in HCC tissues of the H­ras12V­tg mouse and human subjects, as demonstrated using western blotting or immunohistochemical analysis, with the BRD2 autoantibody. In addition, the truncated BRD2 reactive to the BRD2 autoantibody was detected in tumor cell­derived exosomes, which possibly activated TA immune responses and the generation of autoantibodies. For the detection of the serum BRD2 autoantibody, epitope mimicries of autoantigenic BRD2 were screened from a random cyclic peptide CX7C library with the BRD2 autoantibody. A mimotope with the sequence of CTSVFLPHC, which was cyclized by one pair of cysteine residues, exhibited high affinity to the BRD2 autoantibody and competitively inhibited the binding of the autoantibody to the cellular BRD2 antigen. The use of this cyclic peptide as a capture antigen in human serum enzyme­linked immunosorbent assay allowed the distinction of patients with HCC from healthy subjects with 64.41% sensitivity and 82.42% specificity (area under the ROC curve, 0.7761), which is superior to serum alpha­fetoprotein (AFP; 35.83% sensitivity; 100% specificity; area under the ROC curve, 0.5337) for the diagnosis of HCC. In addition, the detection of the BRD2 autoantibody combined with other autoantibody biomarkers or AFP has increased the accuracy of HCC diagnosis, suggesting that the combinational detection of cancer biomarkers, including the BRD2 autoantibody, is a promising assay for HCC diagnosis.

Variation of the intermaxillary tooth-size relationship in normal occlusion.

The purpose of this study was to explore the intermaxillary tooth-size relationship that is attributed to normal occlusion using multivariate cluster analysis, while simultaneously incorporating the full dentition as a data set. From the central incisor to the second molar, the tooth sizes of 307 subjects (188 males and 119 females; mean age ± standard deviation, 19.9 ± 3.3 years) with normal occlusion were investigated. Tooth-size data were analysed separately for the maxilla and the mandible. When clustering, the partitioning around medoids (PAM) algorithm was performed with the transformed data based on principal component analysis (PCA). After the subjects were classified into four groups, the cluster memberships were cross-classified, and the distribution pattern and intermaxillary tooth-size relationships were explored. Bolton tooth ratio showed a relatively wide range, and this was indicative of the variability in tooth size in subjects with a normal occlusion. However, the patterns of the intermaxillary tooth-size relationship were similar for males and females, and this result was concordant with the findings of the classic Bolton analysis. Using the multivariate approach to analyse the tooth-size data set of an individual patient and then comparing the results with the normal occlusion cluster has possible clinical applications in determining the amount and location of tooth-size control in orthodontics.

Influence of the Depth of the Convolutional Neural Networks on an Artificial Intelligence Model for Diagnosis of Orthognathic Surgery.

The aim of this study was to investigate the relationship between image patterns in cephalometric radiographs and the diagnosis of orthognathic surgery and propose a method to improve the accuracy of predictive models according to the depth of the neural networks. The study included 640 and 320 patients requiring non-surgical and surgical orthodontic treatments, respectively. The data of 150 patients were exclusively classified as a test set. The data of the remaining 810 patients were split into five groups and a five-fold cross-validation was performed. The convolutional neural network models used were ResNet-18, 34, 50, and 101. The number in the model name represents the difference in the depth of the blocks that constitute the model. The accuracy, sensitivity, and specificity of each model were estimated and compared. The average success rate in the test set for the ResNet-18, 34, 50, and 101 was 93.80%, 93.60%, 91.13%, and 91.33%, respectively. In screening, ResNet-18 had the best performance with an area under the curve of 0.979, followed by ResNets-34, 50, and 101 at 0.974, 0.945, and 0.944, respectively. This study suggests the required characteristics of the structure of an artificial intelligence model for decision-making based on medical images.

Comparative Analysis of the Differences in Dentofacial Morphology According to the Tongue and Lip Pressure.

The aim of this study was to evaluate the effects of the tongue and lip pressure on dentofacial morphology. The subjects comprised 194 patients with malocclusion. Anterior and posterior tongue elevation and lip pressures were evaluated using the Iowa Oral Performance Instrument (IOPI) device. The lateral cephalograms of each subject were traced and digitized to perform the analysis. Statistical analysis was used to investigate the relationship between perioral muscle force and the cephalometric variables. Anterior and posterior tongue pressure was both higher in males than in females. No sex difference in lip pressure was observed. The group with a low posterior tongue pressure showed a short ramus height, short posterior facial height, and clockwise-rotated mandible. On the other hand, lip pressure had a significant influence on maxillary incisor angulation. Skeletal pattern was not found to be significantly related with lip pressure. The anterior tongue pressure appeared as a mixed pattern of the two results. Tongue pressure was related to skeletal measurements, such as short posterior facial height, and lip pressure was related to the angulation of the anterior teeth. This study suggests that there may be differences in dentofacial morphology according to the differences in perioral muscle force.

Palatal bone density in adult subjects: implications for mini-implant placement.

OBJECTIVES: To evaluate palatal bone density to allow for better selection of palatal implant anchorage sites. MATERIALS AND METHODS: Computed tomographic (CT) images were obtained from 15 males and 15 females (mean age, 27 years; range, 23-35 years). Bone density was measured in Hounsfield units (HU) at 80 coordinates at regular mediolateral and anteroposterior intervals along the midpalatal suture. RESULTS: Bone densities ranged from 805 to 1247 HU. A significant difference between male and female groups was noted, although no difference was found between left and right sides of individual palates. Palatal bone densities showed a tendency to decrease laterally and posteriorly. The midpalatal area within 3 mm of the midsagittal suture had the densest bone in the entire palate. CONCLUSION: Results suggest that mini-implants for orthodontic anchorage may be effectively placed in most areas with bone density equivalent to the palatal area if they are placed from 3 mm posterior to the incisive foramen and 1 to 5 mm to the paramedian side.

Orthodontic treatment combined with autotransplantation after removal of ameloblastoma.

This article describes the use of indirect skeletal anchorage and autotransplantation in a patient who had an ameloblastoma removed. The mandibular left second and third molars were also extracted. Autogenous bone was grafted after surgical removal of the ameloblastoma, and the mandibular right third permanent molar was transplanted into the extraction space. Orthodontic treatment included a miniscrew to bring the transplanted tooth into good occlusion. Four years after treatment, the patient continued to show good results, with no recurrence of the ameloblastoma.